The artificial sweetener 4,1′,6′-trichloro-4,1′,6′-trideoxy-galactosucrose (sucralose) is derived from sucrose by replacing the hydroxyls in the 4,1′, and 6′ position with chlorine. It is 600 times sweeter than cane sugar, and does not participate in human metabolism, and is one of particular interest for use as low calorie sweetener to replace saccharin in various products, including foods, candy, beverages and orally received medicines such as cough drops. Sucralose has the characteristics of high safety and particularly it exhibits the stability in acid aqueous solution. Owing to these advantages, the sucralose is one of the most popular and stronger sweeteners in the market.
However, according to the molecular structure of the sucralose, a major problem of synthesis sucralose is in the field of how only direct the chlorine atoms to the desired positions, if the competition from other reactivity of the hydroxyls came. The synthesis is further complicated by the fact that the primary hydroxyl in the 6 position is un-substituted in the final product. Until now, a number of different synthetic routes for the preparation of sucralose have been developed that the main synthesis methods are omni-group protection method and mono-group protection method at presence, of which the former is not widely used owing to its low yield, complicated operation, high cost and etc.
Considerable work has been carried out to study the mono-group protection method, all of which involve chlorination of the sucrose in the 4,1′, and 6′ position, such as U.S. Pat. Nos. 4,889,928, 5,449,772, 5,023,329, 4,950,746, which focuses on description the synthesis of sugar-6-acetate, while limited information given on part of chlorinated synthesis. Besides, the U.S. Pat. No. 4,380,476 and GB2079749 disclose that sucralose is acylated at the 6-position and the 4,1′ and 6′ positions and then are chlorinated in the presence of unprotected hydroxy groups at the 2,3,3′ and 4′ positions. The GB2181374A also disclosed the method of using thionyl chloride in pyridine with triaryphosphine oxide to synthesis the sucrose, but the question is that the triaryphosphine oxide is troublesome to remove and recycle. What is more, not only the pyridine is toxic and odorous, but also the reaction condition gives more amounts of black insoluble by-product, therefore, it is difficult to work up.
In view of the shortcomings of the prior art, the inventor of the present invention based on years of experience to conduct extensive researches and experiments, and finally developed an advanced method for preparation of surcalose to overcome the shortcomings of the prior art.